The zeta subunit of the T cell antigen receptor is a limiting component in receptor assembly and is required for the targeting of the T cell antigen receptor to the cell surface. Zeta is differentially regulated relative to the other T cell receptor components as witnessed by its expression in natural killer cells. It is also clear that this subunit undergoes alternative splicing to yield another product that has been characterized in murine cells and termed eta. We have characterized the gene encoding the human zeta subunit. The intron/exon organization of the zeta gene and the sites of transcription initiation have been determined. We have also developed this gene as a genetic marker. The cloning of the zeta gene has provided us with the tools to study the transcription of this gene. Studies are underway aimed towards the determination of the promotor and enhancer elements of the zeta gene. A region at the 3' end of the human zeta gene that is highly homologous to the murine eta exon has been characterized. This has led us to study the expression of this eta -like region and to determine the nucleic acid sequence of this region from a number of other mammalian species. As an extension of our findings we have also been studying the relative expression of zeta and eta on a message and protein level during thymic development.